Anti-cancer agents in medicinal chemistry最新文献

{"title":"N-Degron PROTACs as a Potential Therapeutic Approach for Chronic Myeloid Leukemia.","authors":"Grace Hohman, Mohamed A Eldeeb","doi":"10.2174/0118715206367166241230111659","DOIUrl":"https://doi.org/10.2174/0118715206367166241230111659","url":null,"abstract":"<p><p>Many oncoproteins are important therapeutic targets because of their critical role in inducing rapid cell proliferation, which represents one of the salient hallmarks of cancer. Chronic Myeloid Leukemia (CML) is a cancer of hematopoietic stem cells that is caused by the oncogene BCR-ABL1. BCR-ABL1 encodes a constitutively active tyrosine kinase protein that leads to the uncontrolled proliferation of myeloid cells, which is a hallmark of CML. A current therapeutic approach for the treatment of CML, Tyrosine Kinase Inhibitors (TKIs), effectively inactivates BCR-ABL1 kinase activity; however, drug resistance to TKIs limits the long-term potential for this treatment. Proteolysis Targeting Chimera (PROTAC) has emerged as a promising pharmacological approach for degrading, rather than inhibiting, targeted proteins by harnessing the ubiquitin-proteosome system. This process involves tagging a Protein of Interest (POI) with ubiquitin by the E3 ubiquitin ligases, which subsequently target the protein for proteasomal degradation. The N-end rule or the N-degron concept describes the correlation between the metabolic stability of a protein and the biochemical identity of its N-terminal amino acid. A recent work unveiled that N-degron PROTACs could offer a potential treatment for CML by targeting and degrading BCR-ABL1 proteins. Herein, we present the molecular and biochemical implications for targeting chronic myeloid leukemia.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Evaluation of 5-Oxo-1,2,4-triazole-3-carboxamide Compounds as Promising Anticancer Agents: Synthesis, Characterization, In vitro Cytotoxicity and Molecular Docking Studies.","authors":"Rajitha Balavanthapu, Girija Sastry Vedula","doi":"10.2174/0118715206315373241014101856","DOIUrl":"https://doi.org/10.2174/0118715206315373241014101856","url":null,"abstract":"<p><strong>Background: </strong>Cancer presents a significant global health challenge, necessitating effective treatment strategies. While chemotherapy is widely employed, its non-specific nature can induce adverse effects on normal cells, prompting the exploration of targeted therapies. The 1,2,4-triazole scaffold has emerged as a promising element in anticancer drug development due to its structural diversity and potential to target cancer cells.</p><p><strong>Objective: </strong>This study aims to synthesize and evaluate novel derivatives derived from the 1,2,4-triazole scaffold for their potential as anticancer agents. Molecular docking techniques are employed to investigate the interactions between the designed derivatives and specific cancer-related targets, providing insights into potential underlying mechanisms.</p><p><strong>Methods: </strong>The synthesis involves a three-step process to produce 5-oxo-1,2,4-triazole-3-carboxamide derivatives. Various analytical techniques, including NMR and HRMS, validate the successful synthesis. Molecular docking studies utilize X-ray crystal structures of EGFR and CDK-4 obtained from the Protein Data Bank, employing the Schrödinger suite for ligand preparation and Glide's extra-precision docking modes for scoring.</p><p><strong>Results: </strong>The synthesis yields compounds with moderate to good yields, supported by detailed characterization. Molecular docking scores for the derivatives against EGFR and CDK-4 revealed diverse affinities influenced by distinct substituents. Compounds with hydroxyl, and halogen, substitutions exhibited notable binding affinities, while alkyl and amino substitutions showed varying effects. The 1,2,4-triazole derivatives demonstrated potential for targeted cancer therapy.</p><p><strong>Conclusion: </strong>The study highlights the successful synthesis of 5-oxo-1,2,4-triazole-3-carboxamides and their diverse interactions with cancer-related targets. The findings emphasized the potential of these derivatives as candidates for further development as anticancer agents, offering insights into structure-activity relationships. The 1,2,4-triazole scaffold stands out as a promising platform for advancing cancer treatment with enhanced precision and efficacy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-metastasis Effects and Mechanism of Action of Curcumin Analog (2E,6E)-2,6-bis(2,3-dimethoxybenzylidene) Cyclohexanone (DMCH) on the SW620 Colorectal Cancer Cell Line.","authors":"Nurul Fattin Che Rahim, Yazmin Hussin, Muhammad Nazirul Mubin Aziz, Mas Jaffri Masarudin, Shafinaz Abd Gani, Muhammad Nadeem Akhtar, Nik Mohd Afizan Nik Abd Rahman, Noorjahan Banu Alitheen","doi":"10.2174/0118715206336788241029050155","DOIUrl":"https://doi.org/10.2174/0118715206336788241029050155","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths. Curcumin has been reported to have suppressive effects in CRC and to address the physiological limitations of curcumin, a chemically synthesized curcuminoid analog, known as (2E,6E)-2,6-Bis (2,3-Dimethoxy benzylidine) cyclohexanone (DMCH), was developed and the anti-metastatic and anti-angiogenic properties of DMCH in colorectal cell line, SW620 were examined.</p><p><strong>Methods: </strong>The anti-metastatic effects of DMCH were examined in the SW620 cell line by scratch assay, migration, and invasion assay, while for anti-angiogenesis properties of the cells, the mouse aortic ring assay and Human Umbilical Vein Endothelial Cells (HUVEC) assay were conducted. The mechanism of action was determined by microarray-based gene expression and protein analyses.</p><p><strong>Results: </strong>The wound healing assay demonstrated that wound closure was decreased from 63.63 ± 1.44% at IC25 treatment to 4.54 ± 0.62% at IC50 treatment. Significant (p<0.05) reductions in the percentage of migrated and invaded cells were also observed in SW620, with values of 36.39 ± 3.86% and 44.81 ± 3.54%, respectively. Mouse aortic ring assays demonstrated a significant reduction in the formation of tubes and microvessels. Microarray and protein profiler results revealed that DMCH treatment has modulated several metastases, angiogenesisrelated transcripts, and proteins like Epidermal Growth Factor Receptor (EGFR), TIMP-1 (TIMP Metallopeptidase Inhibitor 1) and Vascular Endothelial Growth Factor (VEGF).</p><p><strong>Conclusion: </strong>DMCH could be a potential anti-cancer agent due to its capability to impede metastasis and angiogenesis activities of the SW620 colorectal cancer cell line in vitro via regulating genes and protein in metastases and angiogenesis-related signalling pathways.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review.","authors":"Meshal Alshamrani","doi":"10.2174/0118715206331002241119145651","DOIUrl":"https://doi.org/10.2174/0118715206331002241119145651","url":null,"abstract":"<p><p>Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, etc. have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Function of Poly (U) Binding Splicing Factor 60 (PUF60) in Disease Regulation.","authors":"Huijuan Chen, Tian Guan, Jingfeng Song, Yihua Chen","doi":"10.2174/0118715206346843241119105519","DOIUrl":"https://doi.org/10.2174/0118715206346843241119105519","url":null,"abstract":"<p><p>The alternative splicing (AS) of pre-mRNA is an important process in controlling the expression of human genes, which can enrich the diversity of the proteome and regulate gene function. On the contrary, aberrant splicing contributes significantly to numerous human diseases progression, including tumors, neurological diseases, metabolic diseases, infections, and immune diseases. The PUF60, a protein related to RNA splicing, plays critical functions in RNA splicing and gene transcription regulation. In addition, it can achieve synergistic binding with U2AF65 on RNA through interactions in the pyrimidine region, promoting the splicing of introns with weak 3'- splice sites and pyrimidine bundles. Nevertheless, an increasing amount of evidence supports that it shows a significant overexpression pattern in the vast majority of cancer cells and is crucial for embryonic development, indicating that PUF60 may hold the post of a potential therapeutic target for such diseases. These studies have significantly increased our interest in PUF60. Thus, we briefly reviewed the structural domain characteristics of the PUF60, splicing mutants of PUF60, and the roles and functions in human diseases, including various cancers, infections of bacterium and viruses, myositis, and Verheij syndrome. Furthermore, the targeted PUF60 inhibitors and boundedness of the current research were elaborated on in the article. The article effectively communicates critical perception and insight, making it a precious resource for those interested in PUF60 research and treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cucurbitacin E Glucoside as an Apoptosis Inducer in Melanoma Cancer Cells by Modulating AMPK/PGK1/PKM2 Pathway.","authors":"Mohammed Abdalla Hussein, Aya Sayed Sallam, Shaza Ahmed Mohamed, Amera Mahmoud Abdel-Rady, Adam Mostafa Maghrabe, Abdelrahman Wahdan Soltan, Hanan Mohamed Abdelhamid, Gaber E Eldesoky, Seikh Mafiz Alam, Mohammad Shahidul Islam","doi":"10.2174/0118715206345600241216053948","DOIUrl":"https://doi.org/10.2174/0118715206345600241216053948","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cucurbitacin E glucoside (CEG), a prominent constituent of Cucurbitaceae plants, exhibits notable effects on cancer cell behavior, including inhibition of invasion and migration, achieved through mechanisms such as apoptosis induction, autophagy, cell cycle arrest, and disruption of the actin cytoskeleton.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Melanoma, the fastest-growing malignancy among young individuals in the United States and the predominant cancer among young adults aged 25 to 29, poses a significant health threat. This study aims to elucidate the apoptotic mechanism of CEG against the melanoma cancer cell line (A375).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study estimated the IC50 of CEG against the A375 cell line and assessed cell viability, apoptosis, and necrosis upon CEG treatment. Additionally, IC50 values of CEG against Phosphoglycerate kinase1 (PGK1) and Pyruvate Kinase M2 (PKM2) were determined at various levels of concentrations. The impact of CEG on intracellular glutathione (GSH) levels and the activity of key enzymes (GR, SOD, GPx, CAT), as well as markers of apoptosis (P53), and cell cycle regulation (cyclin D1, cyclin E2, cdk2, cdk4), were estimated. Finally, the level of AMP-activated protein kinase (AMPK), PGK1, and PKM2 gene expression levels in A375 cells were also evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The IC50 value of CEG against A375 cells was determined to be 41.87 ± 2.47 µg/mL. A375 cells treated with CEG showed a significant increase in the G0/G1 phase and a decrease in the S and G2/M phases, indicating cell cycle arrest and reduced proliferation. Additionally, there was an increase in the sub-G1 peak, suggesting enhanced apoptosis. Additionally, the pharmacological analysis revealed potent inhibitory activity of CEG against both PGK1 and PKM2 gene expression, with IC50 values 27.89, 11.70, 7.43 and 2.74 µg/mL after incubation periods intervals of 30, 60, 90 and 120 minutes, respectively. In In-Silico study, computational simulations showed a strong binding affinity of CEG towards AMPK, PGK1, and PKM2 activities, with estimated binding energy (∆G) values of -6.5, -7.9, and -8.3 kcal/mol, respectively. Furthermore, incubation of A375 cells with CEG (at concentrations of 20.9, 41.87, and 83.74 µg/mL) led to a significant decrease in GSH levels and the activity of GR, SOD, GPx, CAT, cyclin D1, cyclin E2, cdk2, and cdk4. Notably, CEG treatment upregulated AMPK levels while downregulating PGK1 and PKM2 gene expression significantly.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;CEG induces apoptosis in melanoma cancer cells (A375) through various mechanisms, including enhanced production of P53 and MDA, inhibition of key enzymes (GR, SOD, GPx, CAT) involved in oxidative stress defense and production of cell cycle regulating enzymes (cyclin D1, cyclin E2, cdk2, cdk4, and upregulation of AMPK and downregulation PGK1, and PKM2 in A375 tumor cells pathways. The downregulation of PKM2 in CEG-treated A375 c","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Prospectives of Cellular Signaling Role for Mammary Gland Carcinogenesis.","authors":"Monu Kumar Kashyap, Sikma Roy, Shiwani Jaiswal, Shweta Verma, Siddhartha Srivastava, Amit Kumar Nigam, Awadhesh Kumar, Bandana Singh, Ved Prakash Tiwari, Mahima Mahima, Akash Ved, Karuna S Shukla, Namrata Singh","doi":"10.2174/0118715206319933241104100736","DOIUrl":"https://doi.org/10.2174/0118715206319933241104100736","url":null,"abstract":"<p><p>In women globally, breast cancer ranks as the second most frequent cause of cancer-related deaths, making up about 25% of female cancer cases, which is pretty standard in affluent countries. Breast cancer is divided into subtypes based on aggressive, genetic and stage. The precise cause of the problem is still unknown. However, the following significant risk factors have been found: sex, age, heredity, not having children, breastfeeding, elevated hormone levels, and personal lifestyle. The presence or lack of three nuclear receptors ER, PR, and HER2/ERBB2 (triple negative) and the amplification of the HER2/ErbB2 gene are the clinical criteria used to classify breast cancer. Chemotherapy is still the cornerstone of treatment for triple-negative breast cancer (TNBC), even. If, for the first two groups of patients,receptor-specific therapy is used. The most often prescribed chemotherapy agents for the treatment of breast cancer include doxorubicin (DOX), curcumin paclitaxel (PTX), docetaxel (DCX), thioridazine (THZ), disulfiram (DSF), and camptothecin (CPT). Monoclonal antibodies (mAbs) were used in antibody-drug conjugates (ADCs) to bind tumor-associated target antigens selectively and deliver very effective cytotoxic agents. According to recent research, synthetic derivatives effectively combat both MCF- 7 and breast cancer cell lines that are resistant to many drugs. This review provides a wealth of information on the mechanism of action of synthetic derivatives on multidrug-resistant cell lines. This review includes information about how synthetic derivatives affect cancer cells that have developed multidrug resistance during chemotherapy. These mechanisms have been linked to factors such as increased drug efflux, genetic factors, growth factors, increased DNA repair capacity, and elevated xenobiotic metabolism. Because of this, more research is necessary to learn more about the effectiveness of synthetic derivatives against breast cancer and cell lines that are resistant to several drugs. This review aims to find recent prospects of various types of cellular signaling pathways (JAK/STAT, Akt, MAPK, etc.) involved in the progression of breast cancer disorder, and we also study different synthetic and natural drugs that are applied for treating breast cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.","authors":"Sara Sigler, Mohammad Abdel-Halim, Reem K Fathalla, Luciana Madeira Da Silva, Adam B Keeton, Yulia Y Maxuitenko, Kristy L Berry, Gang Zhou, Matthias Engel, Ashraf H Abadi, Gary A Piazza","doi":"10.2174/0118715206318802240821114353","DOIUrl":"10.2174/0118715206318802240821114353","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported that the cGMP-specific PDE5 isozyme is overexpressed in colon adenomas and adenocarcinomas and essential for colon cancer cell proliferation, while PDE5 selective inhibitors (e.g., sildenafil) have been reported to have cancer chemopreventive activity.</p><p><strong>Aim: </strong>This study aimed to determine the anticancer activity of a novel PDE5 inhibitor, RF26, using colorectal cancer (CRC) cells and the role of PDE5 in CRC tumor growth <i>in vivo</i>.</p><p><strong>Objective: </strong>The objective of this study was to characterize the anticancer activity of a novel celecoxib derivative, RF26, in CRC cells previously reported to lack COX-2 inhibition but have potent PDE5 inhibitory activity.</p><p><strong>Methods: </strong>Anticancer activity of RF26 was studied using human CRC cell lines. Effects on cell growth, cGMPdependent protein kinase (PKG) activity, β-catenin levels, TCF/LEF transcriptional activity, cell cycle distribution, and apoptosis were measured. CRISPR/cas9 PDE5 knockout techniques were used to determine if PDE5 mediates the anticancer activity of RF26 and validate PDE5 as a cancer target.</p><p><strong>Results: </strong>RF26 was appreciably more potent than celecoxib and sildenafil to suppress CRC cell growth and was effective at concentrations that activated PKG signaling. RF26 suppressed β-catenin levels and TCF/LEF transcriptional activity and induced G1 cell cycle arrest and apoptosis within the same concentration range. CRISPR/cas9 PDE5 knockout CRC cells displayed reduced sensitivity to RF26, proliferated slower than parental cells, and failed to establish tumors in mice.</p><p><strong>Conclusion: </strong>Further evaluation of RF26 for the prevention or treatment of cancer and studying the role of PDE5 in tumorigenesis are warranted.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"52-62"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Effects of Crocin Nanoparticles Alone or in Combination with Doxorubicin against Hepatocellular Carcinoma <i>In vitro</i>.","authors":"Noha S Basuony, Tarek M Mohamed, Doha M Beltagy, Ahmed A Massoud, Mona M Elwan","doi":"10.2174/0118715206327654240823074318","DOIUrl":"10.2174/0118715206327654240823074318","url":null,"abstract":"<p><strong>Objective: </strong>Crocin (CRO), the primary antioxidant in saffron, is known for its anticancer properties. However, its effectiveness in topical therapy is limited due to low bioavailability, poor absorption, and low physicochemical stability. This study aimed to prepare crocin nanoparticles (CRO-NPs) to enhance their pharmaceutical efficacy and evaluate the synergistic effects of Cro-NPs with doxorubicin (DOX) chemotherapy on two cell lines: human hepatocellular carcinoma cells (HepG2) and non-cancerous cells (WI38).</p><p><strong>Methods: </strong>CRO-NPs were prepared using the emulsion diffusion technique and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Zeta potential, and Fourier transform infrared spectroscopy (FT-IR). Cell proliferation inhibition was assessed using the MTT assay for DOX, CRO, CRO-NPs, and DOX+CRO-NPs. Apoptosis and cell cycle were evaluated by flow cytometry, and changes in the expression of apoptotic gene (P53) and autophagic genes (ATG5 & LC3) were analyzed using real-time polymerase chain reaction.</p><p><strong>Results: </strong>TEM and SEM revealed that CRO-NPs exhibited a relatively spherical shape with an average size of 9.3 nm, and zeta potential analysis indicated better stability of CRO-NPs compared to native CRO. Significantly higher antitumor effects of CRO-NPs were observed against HepG2 cells (IC₅₀ = 1.1 mg/ml and 0.57 mg/ml) compared to native CRO (IC₅₀ = 6.1 mg/ml and 3.2 mg/ml) after 24 and 48 hours, respectively. Annexin-V assay on HepG2 cells indicated increased apoptotic rates across all treatments, with the highest percentage observed in CRO-NPs, accompanied by cell cycle arrest at the G2/M phase. Furthermore, gene expression analysis showed upregulation of P53, ATG5, and LC3 genes in DOX/CRO-NPs co-treatment compared to individual treatments. In contrast, WI38 cells exhibited greater sensitivity to DOX toxicity but showed no adverse response to CRONPs.</p><p><strong>Conclusion: </strong>Although more in vivo studies in animal models are required to corroborate these results, our findings suggest that CRO-NPs can be a potential new anticancer agent for hepatocellular carcinoma. Moreover, they have a synergistic effect with DOX against HepG2 cells and mitigate the toxicity of DOX on normal WI38 cells.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"194-206"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Role of ADAMTS9-AS1 in Various Human Cancers: Molecular Pathogenesis and Clinical Implications.","authors":"Haodong He, Jingjie Yang, Yan Zhou, Xinyan Zheng, Lihan Chen, Zhujun Mao, Chuyuan Liao, Tongtong Li, Haoran Liu, Gang Zhou, Houdong Li, Chengfu Yuan","doi":"10.2174/0118715206359325241119075640","DOIUrl":"10.2174/0118715206359325241119075640","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) is a type of non-coding RNA distinguished by a length exceeding 200 nucleotides. Recent studies indicated that lncRNAs participate in various biological processes, such as chromatin remodeling, transcriptional and post-transcriptional regulation, and the modulation of cell proliferation, death, and differentiation, hence influencing gene expression and cellular function. ADAMTS9-AS1, an antisense long non-coding RNA situated on human chromosome 3p14.1, has garnered significant interest due to its pivotal involvement in the advancement and spread of diverse malignant tumors. ADAMTS9-AS1 functions as a competitive endogenous RNA (ceRNA) that interacts with multiple microRNAs (miRNAs) and plays a crucial role in regulating gene expression and cellular functions by modulating essential signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Ras/MAPK pathways. Dysregulation of this factor has been linked to tumor development, migration, invasion, and resistance to apoptotic mechanisms, including as iron-induced apoptosis, underscoring its intricate function in cancer pathology. While current research has clarified certain pathways involved in cancer formation, additional clinical and <i>in vivo</i> investigations are necessary to enhance comprehension of its specific involvement across various cancer types. This review encapsulates the recent discoveries on the correlation of ADAMTS9-AS1 with numerous malignancies, clarifying its molecular mechanisms and its prospective role as a therapeutic target in oncology. Furthermore, it identifies ADAMTS9-AS1 as a potential early diagnostic biomarker and therapeutic target, offering novel opportunities for targeted intervention in oncology.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"533-543"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}